Suzanne Kamel-Reid

Suzanne Kamel-Reid, PhD

Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre
Keywords: leukemia, head and neck cancers, comparative genomic hybridization (CGH), spectral karyotyping, lovastatin, acute promyelocytic leukemia (APL)
Identifying biomarkers of cancer initiation, progression and recurrence

Work in my laboratory focuses on the application of high throughput technologies (e.g., gene expression microarrays, tissue arrays, ChIP-on-chip, microRNA arrays, protein arrays) to enhance our understanding of cancer biology. Specifically, we are interested in identifying biomarkers of cancer initiation, progression and recurrence in two types of human cancer: head and neck squamous cell carcinoma (HNSCC) and acute promyelocytic leukemia (APL).
  • Head and neck squamous cell carcinoma
    In this arm of my research laboratory, we are specifically interested in the etiology of oral cancers (OSCCs). The molecular genetic changes involved in oral cancer development are poorly understood. Our work focuses on three major questions:
    1. What are the gene(s) involved in recurrence of oral cancer? Approximately 50% of OSCCs recur after surgery. Our current approaches involve analyzing OSCC tumour samples, as well as samples taken from the regions immediately surrounding the tumours at time of surgery (''surgical resection margins'') in order to identify genes deregulated in the tumour and in the surrounding margin(s), which may be predictive of tumour recurrence.
    2. What are the steps involved in the development of oral cancer? A significant fraction of OSCCs arise from precursor lesions called leukoplakias. In these studies, we are interested in profiling the genetic changes—specifically, changes in microRNA expression—in leukoplakias and comparing them to genetic changes found in tumours.
    3. What are the underlying genetic differences between OSCCs in young patients (<45 yrs of age) and older patients (>45 yrs of age)? OSCCs are strongly associated with the risk factors of alcohol consumption and smoking tobacco. However, younger patients who do not exhibit exposure to either of these two risk factors are still diagnosed with OSCC. Our previous work has demonstrated that genetic differences exist between young and older patients. Specifically, we have observed defective DNA mismatch repair and differential gene expression in young patients compared to older patients. This line of study is aimed at further understanding the genetic differences between young and older patients, and at understanding the role of defective DNA repair in OSCCs.
  • Acute promyelocytic leukemia
    Leukemias are often associated with chromosomal translocations that give rise to fusion proteins which may deregulate cellular signaling or transcription. Our group cloned and characterized two variant fusion proteins involved in acute promyelocytic leukemia (APL), NPM-RAR-alpha and NuMA-RAR-alpha, which are both aberrant transcription factors; we are especially interested in understanding the roles of these fusion proteins in the cell. Specifically, we use cell lines, mouse models and human patient samples in order to understand leukemia biology. The questions we are most interested in include:
    1. What are the cell biology effects of the APL fusion proteins? While most studies have focused on the APL fusions as transcription factors, more recent evidence has suggested that these proteins behave distinctly and have effects through protein-protein interactions on other signaling pathways within the leukemic cell. We are applying the same concept as above, and hypothesizing that there may be a common set of interactions and/or deregulated pathways shared by all APL fusion proteins, and are characterizing the protein-protein interactions of the fusions in order to find this out.
    2. What are the necessary secondary events in leukemia development? Previous studies have indicated that the APL fusions are necessary, but insufficient, for the development of leukemia in mice. This suggests that additional genetic ''events'' may cooperate with the fusions in leukemia. We are addressing this question through the above studies, and also through genetic studies of the hCG-NuMA-RAR-alpha mouse model that we previously developed and characterized.
    What are the common downstream genetic targets of the APL fusion proteins? APL is associated with seven known fusion proteins, all of which involve the RAR-alpha transcription factor. Yet, all fusion proteins give rise to the same disease. We hypothesize that this is because all fusion proteins have a common set of direct transcriptional targets, and are utilizing gene expression arrays and ChIP-on-chip technology to address this issue.
Sustained deep molecular responses in patients switched to nilotinib due to persistent BCR-ABL1 on imatinib: final ENESTcmr randomized trial results.
Leukemia. 2017 Aug 03;:
Hughes TP, Leber B, Cervantes F, Spector N, Pasquini R, Clementino NCD, Schwarer AP, Dorlhiac-Llacer PE, Mahon FX, Rea D, Guerci-Bresler A, Kamel-Reid S, Bendit I, Acharya S, Glynos T, Dalal D, Branford S, Lipton JH
Prognostic and predictive effects of TP53 co-mutation in patients with EGFR-mutated non-small cell lung cancer (NSCLC).
Lung Cancer. 2017 Sep;111:23-29
Labbé C, Cabanero M, Korpanty GJ, Tomasini P, Doherty MK, Mascaux C, Jao K, Pitcher B, Wang R, Pintilie M, Leighl NB, Feld R, Liu G, Bradbury PA, Kamel-Reid S, Tsao MS, Shepherd FA
Improving validation methods for molecular diagnostics: application of Bland-Altman, Deming and simple linear regression analyses in assay comparison and evaluation for next-generation sequencing.
J Clin Pathol. 2017 Jul 26;:
Misyura M, Sukhai MA, Kulasignam V, Zhang T, Kamel-Reid S, Stockley TL
Uncommon EGFR mutations in advanced non-small cell lung cancer.
Lung Cancer. 2017 Jul;109:137-144
O'Kane GM, Bradbury PA, Feld R, Leighl NB, Liu G, Pisters KM, Kamel-Reid S, Tsao MS, Shepherd FA
Integration of Technical, Bioinformatic, and Variant Assessment Approaches in the Validation of a Targeted Next-Generation Sequencing Panel for Myeloid Malignancies.
Arch Pathol Lab Med. 2017 Jun;141(6):759-775
Thomas M, Sukhai MA, Zhang T, Dolatshahi R, Harbi D, Garg S, Misyura M, Pugh T, Stockley TL, Kamel-Reid S
Circulating tumour DNA sequence analysis as an alternative to multiple myeloma bone marrow aspirates.
Nat Commun. 2017 May 11;8:15086
Kis O, Kaedbey R, Chow S, Danesh A, Dowar M, Li T, Li Z, Liu J, Mansour M, Masih-Khan E, Zhang T, Bratman SV, Oza AM, Kamel-Reid S, Trudel S, Pugh TJ
Management of EGFR-mutated non-small-cell lung cancer: practical implications from a clinical and pathology perspective.
Curr Oncol. 2017 Apr;24(2):111-119
Cabanero M, Sangha R, Sheffield BS, Sukhai M, Pakkal M, Kamel-Reid S, Karsan A, Ionescu D, Juergens RA, Butts C, Tsao MS
Improving molecular testing and personalized medicine in non-small-cell lung cancer in Ontario.
Curr Oncol. 2017 Apr;24(2):103-110
Lim C, Sekhon HS, Cutz JC, Hwang DM, Kamel-Reid S, Carter RF, Santos GDC, Waddell T, Binnie M, Patel M, Paul N, Chung T, Brade A, El-Maraghi R, Sit C, Tsao MS, Leighl NB
Consistency and reproducibility of next-generation sequencing and other multigene mutational assays: A worldwide ring trial study on quantitative cytological molecular reference specimens.
Cancer. 2017 May 05;:
Malapelle U, Mayo-de-Las-Casas C, Molina-Vila MA, Rosell R, Savic S, Bihl M, Bubendorf L, Salto-Tellez M, de Biase D, Tallini G, Hwang DH, Sholl LM, Luthra R, Weynand B, Vander Borght S, Missiaglia E, Bongiovanni M, Stieber D, Vielh P, Schmitt F, Rappa...
Treatment options for patients with brain metastases from EGFR/ALK-driven lung cancer.
Radiother Oncol. 2017 Mar 28;:
Doherty MK, Korpanty GJ, Tomasini P, Alizadeh M, Jao K, Labbé C, Mascaux CM, Martin P, Kamel-Reid S, Tsao MS, Pintilie M, Liu G, Bradbury PA, Feld R, Leighl NB, Chung C, Shepherd FA

Pages


 
Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre

Professor, Departments of Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto
Head, Laboratory Genetics, University Health Network
Director, Molecular Diagnostics, University Health Network
Member, Ontario Genetics Secretariat Executive
Co-chair, Molecular Oncology Advisory Committee, Cancer Care Ontario​